Giant cell tumors

1. GIANT CELL TUMOR
CHONDROBLASTOMA

2. GIANT CELL TUMOR
• Giant cell tumor of bone is a distinctive neoplasm of undifferentiated cells.
• The multinucleated giant cells apparently result from fusion of the proliferating
mononuclear cells, and although they are a constant and prominent part of these
tumors, the giant cells are probably of less signifi cance than the mononuclear cells.
• Giant cell tumors usually are solitary lesions; however, 1% to 2% may be
synchronously or metachronously multicentric.
• It is unclear whether multicentric disease represents multiple primary lesions or
simply bone metastases from a single primary lesion.
• Although these tumors typically are benign, pulmonary metastases occur in
approximately 3% of patients.
• The overall mortality rate from disease for patients with pulmonary metastases is
approximately 15%.

3. • Malignant giant cell tumors represent less than 5% of cases and are classified as
primary or secondary.
• Primary malignant giant cell tumors are extremely rare and are defined as
sarcomas that occur within lesions that otherwise are typical of benign giant cell
tumors.
• Secondary malignant giant cell tumors are sarcomas that occur at the sites of giant
cell tumors that have been treated, usually with radiation.
In fact, these osteoclast-like giant cells, with or without modification , occur in many
pathologic conditions of bone,such as
• aneurysmal bone cyst,
• benign chondroblastoma,
• chondromyxoid fibroma,
• unicameral bone cyst with a cellular lining,
• metaphyseal fibrous defect,
• giant cell reparative granuloma,
• hyperparathyroidism,
• giant cell-containing osteosarcoma, and other entities in the general category of
giant cell tumor.

4. • 5% of neoplasms of bone.
• occur in patients 20 to 40 years old, and there is a slight female
predominance.

5. LOCATION
• Most giant cell tumors are found at the ends (epiphyses) of
long bones.
• Approximately 46.2% of the lesions occurred around the knee
joint, with the distal femur being the most common single
location.
• 3rd – distal end of radius
• 4th –sacrum
• Vertebrae –mostly variants.

6. SYMPTOMS
• Pain of variable severity is almost always the
predominant symptom.
• The pain is rarely severe, unless a pathologic fracture
has occurred. In 10% to 30% of patients, pathologic
fractures are evident at initial examination.
• More than three-fourths of the patients had noted
swelling of the affected region.
• Less common symptoms included weakness, limitation
of motion of the joint, and signs of pathologic fracture.

7. PHYSICAL FINDINGS
• A hard, sometimes crepitant and painful mass
is found in more than 80% of the patients.
• Atrophy of muscles from disuse may be
present as well as effusion in the adjacent
joint or local rise in temperature .

8. RADIOGRAPHIC FEATURES
• Gee and Pugh summarized the radiographic
featuresas those of an expanding zone of
radiolucency situated eccentrically, usually in the
epiphyses of long bones and usually abut the
subchondral bone of an adult.
• The lesion usually extends to the articular cartilage,
although there may be a thin zone of normal bone
between the lesion and the articular cartilage.
• The lesion may be well marginated or poorly
marginated.
• It is unusual to see sclerosis around a benign giant
cell tumor.
• Radiographically, the lesions are purely lytic. The
zone of transition can be poorly defined on plain
radiographs.

10. The tumor frequently destroys the cortex and
extends into the soft tissue.

11. On MRI, the lesion
usually is dark on T1-
weighted images
and bright on T2-
weighted images. MRI
also may reveal
fluid-fluid levels typical
of a secondary
aneurysmal bone cyst,
which occurs in 20% of
patients.

12. GROSS PATHOLOGIC FEATURES
• The tumor tissue is characteristically soft, friable, and dark
brown.
• Firmer portions may be seen as a result of previous fracture,
treatment, or degeneration, all of which may cause fi brosis
and osteoid production.
• Small cystic or necrotic portions, sometimes filled with blood,
may be present, but these ordinarily constitute an insignificant
feature of untreated lesions not modified by previous fracture.
• This cystification may be sufficiently prominent, especially in
recurrent neoplasms, to cause them to be confused with
aneurysmal bone cyst.
• The aggressive nature of giant cell tumors accounts for the
usually immense size when they have been neglected.
• Intact gross specimens show variable degrees of expansion of
the bone with corresponding expansion or destruction of the
cortex. The rest of the osseous structure in the region of the
tumor is completely replaced.
• The tumor practically always extends to the articular cartilage,
and its boundaries are only moderately well demarcated from
adjacent bone and cartilage. Even with very large lesions, the
periosteum is rarely breached

13. Typical giant cell tumor involving the distal radius, the third most common location.
A: The tumor is purely lytic and has expanded into soft tissue. There is a pathologic fracture.
B: Gross specimen. The cortices have been destroyed, and the lesion expands into soft tissue.
The tumor also extends up to the articular cartilage.

14. Giant cell tumor forming a destructive redbrown mass involving the entire distal femur.
The cystic areas represent a secondary aneurysmal bone cyst component.

15. Recurrent giant cell tumor involving the thigh.
When giant cell tumor recurs in the soft tissue, it is usually well circumscribed and is
enclosed by a shell of ossification. The lesion has the typical appearance of giant cell tumor.

16. Giant cell tumor of the proximal tibia. The tumor has the characteristic red-brown color of giant
cell tumor with a central golden yellow area that corresponds with degenerative necrosis.

17. HISTOPATHOLOGIC FEATURES
• The basic proliferating cells have a round-to-oval
or even spindle-shaped nucleus in the fi elds that
are diagnostic of true giant cell tumor.
• This nucleus is surrounded by an ill-defi ned
cytoplasmic zone, and discernable intercellular
substance is absent.
• Mitotic figures can be found in practically every
lesion, and in some lesions, they are numerous.
Mitotic activity has no prognostic signifi cance.
• The nuclei lack the hyperchromatism and
variation in size and shape that are characteristic
of sarcoma.
• Giant cells, usually containing 40 to 60 nuclei, are
scattered uniformly throughout the lesion. The
evidence that the giant cells are derived from
fusion of mononuclear cells includes some marked
similarity of their nuclei.

18. Nuclei of the mononuclear cells are very similar
to the nuclei of the giant cells, so that it may be
hard to tell where the giant cells stop and the
mononuclear cells begin
Mitotic figures are commonly
found in the mononuclear cells.
This field contains at least four
mitotic figures.

19. TREATMENT
• Historically, treatment consisted of simple curettage; however, subsequent
recurrence rates were greater than 50%.
• Now, most published series document recurrence rates of 5% to 15%.
• The decrease in recurrence rates probably can be attributed to several
factors:
 MRI now allows for more accurate assessment of the extent of lesions,
and the technique of curettage has improved.
 It is important to create a cortical window that is at least as large as the
lesion to prevent leaving residual tumor cells “around the corner”
adjacent to the near-side cortex. Also, use of a power burr to enlarge the
cavity 1 to 2 cm in all directions is now considered standard.
• Care should be taken, however, to avoid perforation through the
subchondral bone into the joint.

20. • The use of adjuvants, such as liquid nitrogen, phenol, bone cement,
electrocautery, or an argon beam coagulator, theoretically helps kill any
remaining tumor cells.
• Also, preliminary studies suggest that bisphosphonates (administered
systemicallor locally) might help prevent recurrence.
• To fill the defect after curettage, the surgeon has several options, including
autograft bone, allograft bone, an artificial bone graft substitute, or
methyl methacrylate bone cement.
• If an autograft is to be harvested from another site, separate gloves and
instruments should be used because cross-contamination could lead to
transplantation of tumor cells to the harvest site.
• A bone graft (or artificial substitute) has the theoretical advantage of
restoring normal biomechanics to the joint surface to prevent future
degenerative joint disease and restoring bone stock, which may help if
future procedures are necessary.

28. MEDICAL MANAGEMENT
• There is clinical rationale for the use of bisphosphonates in treating giant cell
tumor of bone, as these drugs inhibit osteoclastic activity and promote osteoclast
apoptosis.
• Studies using systemic zoledronic acid in inoperable tumors have reported
stabilization of both local and metastatic disease.
• Bisphosphonates have been proposed for use as a surgical adjuvant or as an
option in unresectable tumors; however, high-level evidence is still lacking, and
further investigation is required to validate its use.
• Another new treatment under examination is the systemic administration of
denosumab. Denosumab is a fully human monoclonal antibody that inhibits
normal and tumorassociated bone lysis by limiting osteoclastic maturation (i.e.,
prevents activation of receptor activator of nuclear factorkB [RANK]).
• This drug has approval from the US Food and Drug Administration for use in adults
and skeletally mature patients who have an unresectable giant cell tumor or a
condition in which surgical resection would result in severe morbidity.

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